Vol. 286, Issue 2, 841-847, August 1998

Murine Alpha₁-Adrenoceptor Subtypes. I. Radioligand Binding Studies¹

Ming Yang, Jens Reese, Susanna Cotecchia and Martin C. Michel

Department of Medicine, University of Essen, Essen, Germany (M.Y., J.R., M.C.M.), and the Department of Pharmacology, University of Lausanne, Lausanne, Switzerland (S.C.)

Alpha₁-adrenoceptors were identified in murine tissues by [³H]prazosin saturation binding studies, with a rank order of cerebral cortex > cerebellum > liver > lung > kidney > heart > spleen, with the spleen not exhibiting detectable expression. Competition binding studies were performed with 5-methylurapidil, BMY 7378, methoxamine, (+)-niguldipine, noradrenaline, SB 216469 and tamsulosin. On the basis of monophasic low-affinity competition by BMY 7378, alpha_1D-adrenoceptors were not detected at the protein level in any tissue. On the basis of competition studies with the alpha_1A/alpha_1B-discriminating drugs, alpha_1B-adrenoceptors appeared to be the predominant or even the sole subtype in murine liver, lung and cerebellum, whereas murine cerebral cortex and kidney contained ~30% and 50% of alpha_1A-adrenoceptors, respectively. The affinities of the various competitors in the murine tissues were quite similar to those reported from other species. The ratio of high- and low-affinity sites for tamsulosin did not in all cases match the percentages of alpha_1A- and alpha_1B-adrenoceptors detected by the other competitors; however, the low-affinity component of the tamsulosin competition curves was abolished in the cerebral cortex of alpha_1B-adrenoceptor knockout mice. Treatment with chloroethylclonidine (10 µM, 30 min, 37°C) inactivated the alpha₁-adrenoceptors in all tissues by >75%. When the concentration-dependent inactivation of tissue alpha_1B-adrenoceptors (liver) and tissue alpha_1A-adrenoceptors (cerebral cortex from alpha_1B-adrenoceptor knockout mice) was compared, alpha_1A-adrenoceptors were only slightly less sensitive toward chloroethylclonidine than alpha_1B-adrenoceptors. We conclude that murine tissues express alpha_1A- and alpha_1B-adrenoceptors, which are largely similar to those in other species. However, the tissue-specific distribution of subtypes may differ from that of other species.